In the current project, genetic determinants of non-renal complications of diabetes and related traits are being sought using techniques of genetic linkage and association analysis. (For a report on renal complications see Genetic Epidemiology of Diabetic Nephropathy DK069094-04.) Lymphoblast cell lines have been established from informative pedigrees. DNA is available from other families in nuclear pellets extracted from blood specimens obtained in the epidemiologic studies. Families with many diabetic members have been ascertained through the epidemiologic studies and most have participated in studies of genetics of diabetes or nephropathy (see also Genetic Epidemiology of Diabetes and Obesity DK069028-22). Some families have been studied in collaboration with the multicenter Family Investigation of Nephropathy and Diabetes (FIND). Genome-wide linkage studies of total cholesterol levels in the Pimas have identified strong evidence for linkage on chromosome 19p. A genome-wide association study conducted as part of the multicenter Family Investigation of Nephropathy and Diabetes is currently being analyzed to identify potential retinopathy susceptibility variants. We have also begun to assess candidate genes for retinopathy and glycemic control in regions implicated by genome-wide association studies in other populations to determine the extent of association in Pima Indians. Analyses of several candidate polymorphisms to date show little evidence of association in Pimas. Current studies involve systematic surveys of candidate genes in the chromosome 19p region linked to total cholesterol levels. Periodontitis has also been assessed in these pedigrees and linkage and association analyses are currently being conducted. Association with diabetic retinopathy will also be assessed in individuals who participated in the FIND genome-wide association study for nephropathy;genotyping for this study is ongoing.